The objective of this grant is to complete studies in process of the neurological, psychological, biochemical, and electroencephalographic effects of large doses of vitamin B6, started in the neonatal period and administered continuously, upon central nervous system function in patients with the trisomy 21 form of Down's syndrome. A double blind protocol is underway with half the patients receiving placebo and the other half receiving from 12.5 to 35.5 mg/kg of vitamin B6 daily. The code is broken when each patient reaches three years of age; to date, the code breaking procedure has been accomplished in four patients. Another objective of this study is to determine the occurrence of any side effects that may result from the longterm use of these doses of the vitamin in young patients. In addition, both in vivo and in vitro studies of pyridoxine metabolism are under investigation. The role of pyridoxine leukocyte phosphate (PLP) in the plasma and the red cells and 4-pyridoxic acid (4PA, in twenty four hour urine specimens of trisomy 21 patients receiving either vitamin B6 or placebo is being studied. It is hoped this research project will give a definite answer to the question "Is vitamin B6 of therapeutic value to patients with Down's syndrome?" It will also examine the mechanisms of pyridoxine metabolism in such patients.